Kilpinen Lotta, Parmar Amarjit, Greco Dario, Korhonen Matti, Lehenkari Petri, Saavalainen Päivi, Laitinen Saara
Research and Development, Finnish Red Cross Blood Service, Helsinki, 00310, Finland.
Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, 00014, Finland.
Aging (Albany NY). 2016 Nov 9;8(11):2799-2813. doi: 10.18632/aging.101088.
Mesenchymal stromal cells (MSC) are currently used in many cell based therapies. Prior to use in therapy, extensive expansion is required. We used microarray profiling to investigate expansion induced miRNA and mRNA expression changes of bone marrow MSCs (BM-MSCs) derived from old and young donors. The expression levels of 36 miRNAs were altered in cells derived from the old and respectively 39 miRNAs were altered in cells derived from young donors. Of these, only 12 were differentially expressed in both young and old donor BM-MSCs, and their predicted target mRNAs, were mainly linked to cell proliferation and senescence. Further qPCR verification showed that the expression of miR-1915-3p, miR-1207, miR-3665, and miR-762 correlated with the expansion time at passage 8. Previously described BM-MSC-specific miRNA fingerprints were also detected but these remained unchanged during expansion. Interestingly, members of well-studied miR-17/92 cluster, involved in cell cycle regulation, aging and also development of immune system, were down-regulated specifically in cells from old donors. The role of this cluster in MSC functionality is worth future studies since it links expansion, aging and immune system together.
间充质基质细胞（MSC）目前被用于多种基于细胞的治疗方法中。在用于治疗之前，需要进行大量扩增。我们使用微阵列分析来研究来自老年和年轻供体的骨髓间充质干细胞（BM-MSC）在扩增诱导下的miRNA和mRNA表达变化。来自老年供体的细胞中有36种miRNA的表达水平发生了改变，来自年轻供体的细胞中有39种miRNA的表达水平发生了改变。其中，只有12种在年轻和老年供体的BM-MSC中差异表达，其预测的靶mRNA主要与细胞增殖和衰老相关。进一步的qPCR验证表明，miR-1915-3p、miR-1207、miR-3665和miR-762的表达与第8代的扩增时间相关。之前描述的BM-MSC特异性miRNA指纹也被检测到，但在扩增过程中保持不变。有趣的是，参与细胞周期调控、衰老以及免疫系统发育的研究充分的miR-17/92簇成员，在来自老年供体的细胞中特异性下调。由于该簇将扩增、衰老和免疫系统联系在一起，其在MSC功能中的作用值得未来研究。
